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5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models

Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and...

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Autores principales: Angelino, Donato, Carregosa, Diogo, Domenech-Coca, Cristina, Savi, Monia, Figueira, Inês, Brindani, Nicoletta, Jang, Saebyeol, Lakshman, Sukla, Molokin, Aleksey, Urban, Joseph F., Davis, Cindy D., Brito, Maria Alexandra, Kim, Kwang Sik, Brighenti, Furio, Curti, Claudio, Bladé, Cinta, del Bas, Josep M., Stilli, Donatella, Solano-Aguilar, Gloria I., dos Santos, Claudia Nunes, del Rio, Daniele, Mena, Pedro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893823/
https://www.ncbi.nlm.nih.gov/pubmed/31694297
http://dx.doi.org/10.3390/nu11112678
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author Angelino, Donato
Carregosa, Diogo
Domenech-Coca, Cristina
Savi, Monia
Figueira, Inês
Brindani, Nicoletta
Jang, Saebyeol
Lakshman, Sukla
Molokin, Aleksey
Urban, Joseph F.
Davis, Cindy D.
Brito, Maria Alexandra
Kim, Kwang Sik
Brighenti, Furio
Curti, Claudio
Bladé, Cinta
del Bas, Josep M.
Stilli, Donatella
Solano-Aguilar, Gloria I.
dos Santos, Claudia Nunes
del Rio, Daniele
Mena, Pedro
author_facet Angelino, Donato
Carregosa, Diogo
Domenech-Coca, Cristina
Savi, Monia
Figueira, Inês
Brindani, Nicoletta
Jang, Saebyeol
Lakshman, Sukla
Molokin, Aleksey
Urban, Joseph F.
Davis, Cindy D.
Brito, Maria Alexandra
Kim, Kwang Sik
Brighenti, Furio
Curti, Claudio
Bladé, Cinta
del Bas, Josep M.
Stilli, Donatella
Solano-Aguilar, Gloria I.
dos Santos, Claudia Nunes
del Rio, Daniele
Mena, Pedro
author_sort Angelino, Donato
collection PubMed
description Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-γ-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-γ-valerolactone-sulfate (3′,4′ isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the “gut-brain axis”.
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spelling pubmed-68938232019-12-23 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models Angelino, Donato Carregosa, Diogo Domenech-Coca, Cristina Savi, Monia Figueira, Inês Brindani, Nicoletta Jang, Saebyeol Lakshman, Sukla Molokin, Aleksey Urban, Joseph F. Davis, Cindy D. Brito, Maria Alexandra Kim, Kwang Sik Brighenti, Furio Curti, Claudio Bladé, Cinta del Bas, Josep M. Stilli, Donatella Solano-Aguilar, Gloria I. dos Santos, Claudia Nunes del Rio, Daniele Mena, Pedro Nutrients Article Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-γ-valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-γ-valerolactone-sulfate (3′,4′ isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the “gut-brain axis”. MDPI 2019-11-05 /pmc/articles/PMC6893823/ /pubmed/31694297 http://dx.doi.org/10.3390/nu11112678 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Angelino, Donato
Carregosa, Diogo
Domenech-Coca, Cristina
Savi, Monia
Figueira, Inês
Brindani, Nicoletta
Jang, Saebyeol
Lakshman, Sukla
Molokin, Aleksey
Urban, Joseph F.
Davis, Cindy D.
Brito, Maria Alexandra
Kim, Kwang Sik
Brighenti, Furio
Curti, Claudio
Bladé, Cinta
del Bas, Josep M.
Stilli, Donatella
Solano-Aguilar, Gloria I.
dos Santos, Claudia Nunes
del Rio, Daniele
Mena, Pedro
5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models
title 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models
title_full 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models
title_fullStr 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models
title_full_unstemmed 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models
title_short 5-(Hydroxyphenyl)-γ-Valerolactone-Sulfate, a Key Microbial Metabolite of Flavan-3-ols, Is Able to Reach the Brain: Evidence from Different in Silico, In Vitro and In Vivo Experimental Models
title_sort 5-(hydroxyphenyl)-γ-valerolactone-sulfate, a key microbial metabolite of flavan-3-ols, is able to reach the brain: evidence from different in silico, in vitro and in vivo experimental models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893823/
https://www.ncbi.nlm.nih.gov/pubmed/31694297
http://dx.doi.org/10.3390/nu11112678
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